Professor Shouqing Luo
Profiles

Professor Shouqing Luo

Professor of Neurobiology

Peninsula Medical School (Faculty of Health)

Professor Shouqing Luo can be contacted through arrangement with our Press Office, to speak to the media on these areas of expertise.
  • Dementia
  • Clinical trials
  • Neuroscience
  • Neurodegenerative disease
  • Huntington’s disease 
  • Autophagy
  • The brain
Biography

Biography

Professor of Neurobiology

Peninsula Medical School (Faculty of Health), University of Plymouth

Qualifications


Senior Research Fellow
Cambridge Institute for Medical Research
University of Cambridge, UK


Research Fellow
Cambridge Institute for Medical Research
University of Cambridge, UK


Postdoctoral Research Associate
Northwestern University Medical School, USA


Research Fellow
National Institute of Child Health and Human Development
National Institutes of Health (NIH), USA

PhD, Peking Union Medical College & Chinese Academy of Medical Sciences, China 

Professional membership

British Society of Biochemistry
British Society of Cell Biology
American Society of Biochemistry and Molecular Biology

Roles on external bodies

Associate Editor, Autophagy

Key publications

Luo S, Garcia-Arencibia M, Zhao R, Puri C, Toh PPC, Sadiq O & Rubinsztein DC (2012) 'Bim inhibits autophagy by recruiting Beclin 1 to microtubules' Molecular Cell 47, (3) 359-370 , DOI
Luo S & Rubinsztein DC (2009) 'Apoptosis blocks Beclin 1-dependent autophagosome synthesis - an effect rescued by Bcl-xL' Cell Death and Differentiation 17, 268-277 , DOI
Luo S, Vacher C, Davies JE & Rubinsztein DC (2005) 'Cdk5 phosphorylation of huntingtin reduces its cleavage by caspases: implications for mutant huntingtin toxicity' Journal of Cell Biology 169, 647-656
Li Z, Wang C, Wang Z, Zhu C, Li J, Sha T, Ma L, Gao C, Yang Y & Sun Y (2019) 'Allele-selective lowering of mutant HTT protein by HTT–LC3 linker compounds' Nature 575, (7781) 203-209 , DOI Open access
Yang Y, Willis TL, Button RW, Strang CJ, Fu Y, Wen X, Grayson PRC, Evans T, Sipthorpe RJ & Roberts SL (2019) 'Cytoplasmic DAXX drives SQSTM1/p62 phase condensation to activate Nrf2-mediated stress response' Nature Communications 10, (1) 0-0 , DOI Open access
Yu M, Fu Y, Liang Y, Song H, Yao Y, Wu P, Yao Y, Pan Y, Wen X & Ma L (2017) 'Suppression of MAPK11 or HIPK3 reduces mutant Huntingtin levels in Huntington's disease models' Cell Research 27, (12) 1441-1465 , DOI Open access
View all publications
Teaching

Teaching

Teaching interests

HEA Fellow

Clinical Neurobiology

Current Issues in Neurobiology

Placement and Employability

Academic tutor of Special Study Unit

Director of Postgraduate Studies

Staff serving as external examiners

University of Cambridge

University of Liverpool

University College London

Research

Research

Research interests

Macroautophagy or autophagy is an intracellular bulk degradation system mediated by lysosomes. Autophagy substrates include long-lived cytosolic proteins, intracellular pathogens and damaged organelles. Autophagosomes are then fused to lysosomes and the contents of autophagosomes are degraded by lysosomal hydrolases, and the resulting degraded components are reused for anabolic and catabolic processes. Autophagy is involved in many biological processes of normal physiology, such as mitigating metabolic stress, degradation of aggregate-prone proteins (e.g, mutant huntingtin), tissue homeostasis, and defects in autophagy process are associated with numerous pathophysiologies, including neurodegenerative diseases and tumorigenesis. The research in our lab currently focuses on characterising novel autophagy pathways to tackle neurodegeneration. We are taking on the following research programmes.

1. SQSTM1/p62 phase separation biology - implication in selective autophagy and neurodegeneration

Protein bodies/protein non-membrane structures (e.g. SQSTM1/p62 bodies) represent open macromolecular assemblies at which bio-materials are organised in a dynamic manner. Mounting evidence suggests that these non-membrane compartments are formed as liquid droplets though liquid-liquid phase separation, a process in which bio-macromolecules demix from solution and form a separate liquid phase. Although hundreds of proteins are enriched in protein droplets, only a subset of proteins are believed to promote liquid droplet formation. Protein bodies plays critical roles in ageing and neurodegeneration. It is important to characterise the aetiology of protein body formation. The metazoan autophagy receptor SQSTM1/p62 recognises the cargo via their ubiquitin binding, and it has been best characterised to mediate autophagic clearance of aggregated proteins. p62 body formation is critical for its function as an autophagy receptor. We have recently found that DAXX promotes the phase transition and condensation of p62 to enhance its recruitment of ubiquitinated proteins (Nature Comms, 2019). Based on this work, we are continuing to address p62 phase separation and neurodegeneration.

2. New autophagy approaches to tackle Huntington's disease (HD)

Previously I characterized the BH3-only protein Bim as a dual molecule functioning in both autophagy inhibition and apoptosis induction (Mol Cell, 2012). This has now been widely accepted (follow-up work has been published by other groups numerous journals, e.g. Blood, J Cell Biol, Autophagy, Cell Cycle). Importantly, we found that Bim protein levels are upregulated in the neurons in HD conditions. We hypothesised that Bim may be a driver for HD progression. Recently we characterised that Bim contributes to HD progression (Hum Mol Genet, 2020), and we aim to lower Bim activity to ameliorate HD pathology. 

3. Lipid metabolism in neurodegeneration 

Cholesterol is a lipid essential for mammalian cell membranes. It is known that the brain has a 10-fold higher cholesterol concentration than other tissues. Lipid metabolism is an emerging focus of research into neurodegeneration. We aim to examine if cholesterol esters accumulation contribute to HD neurodegeneration.

Other research

 My Bibliography: https://www.ncbi.nlm.nih.gov/myncbi/1BUtvIaiMVesi2/bibliography/public/

Grants & contracts

Recent funding:

2022-2024. Principal applicant, Rosetrees, PGL21/10002, Lowering autophagosomal overload to mitigate synucleinopathies, £91,256

2020-2022, Principal applicant, the Royal Society, IEC\NSFC\191180 - International Exchanges 2019 Cost Share (NSFC), the autophagy role of lncRNAs, £11,700.00

2019-2022. Newton Advanced Fellowship UK Principal Applicant. The Academy of Medical Sciences/the Royal Society (Newton Fund). Selective autophagy regulation in Huntington's Disease and neurodegeneration (NAF\R1\191045), £111,000

2016-2019. Principal applicant, Medical Research Council. Tackling autophagy and apoptosis for the potential therapy of Huntington’s Disease (MR/M023605/1), £528,993

2018-2021. Principal applicant. BRACE Charity. Mechanisms of mitochondrial dysfunction in neurodegeneration (BR18/01), £85,863

2017-2019. Principal applicant. BRACE Charity. New strategies in alleviation of aggregation-prone protein toxicity in dementia diseases (BR17/04), £58,545

2016-2019. Principal applicant. DTS PhD studentship programme. Identification of a Novel Autophagy Pathway, £72,000

2015-2017. Principal applicant. National Natural Science Foundation of China (NSFC). Selective degradation of autophagy (31428014), RMB200,000

2013-2015. Principal applicant. Northcott Medical Foundation. The mechanism of artemisinin derivatives’ modulation in autophagy and cell death (5002), £7250

2013-2016. Principal applicant. PhD studentship in Translational and Stratified Institute. The interaction between autophagy and cell death, £62,000


Publications

Publications

Key publications

Luo S, Garcia-Arencibia M, Zhao R, Puri C, Toh PPC, Sadiq O & Rubinsztein DC (2012) 'Bim inhibits autophagy by recruiting Beclin 1 to microtubules' Molecular Cell 47, (3) 359-370 , DOI
Luo S & Rubinsztein DC (2009) 'Apoptosis blocks Beclin 1-dependent autophagosome synthesis - an effect rescued by Bcl-xL' Cell Death and Differentiation 17, 268-277 , DOI
Luo S, Vacher C, Davies JE & Rubinsztein DC (2005) 'Cdk5 phosphorylation of huntingtin reduces its cleavage by caspases: implications for mutant huntingtin toxicity' Journal of Cell Biology 169, 647-656
Li Z, Wang C, Wang Z, Zhu C, Li J, Sha T, Ma L, Gao C, Yang Y & Sun Y (2019) 'Allele-selective lowering of mutant HTT protein by HTT–LC3 linker compounds' Nature 575, (7781) 203-209 , DOI Open access
Yang Y, Willis TL, Button RW, Strang CJ, Fu Y, Wen X, Grayson PRC, Evans T, Sipthorpe RJ & Roberts SL (2019) 'Cytoplasmic DAXX drives SQSTM1/p62 phase condensation to activate Nrf2-mediated stress response' Nature Communications 10, (1) 0-0 , DOI Open access
Yu M, Fu Y, Liang Y, Song H, Yao Y, Wu P, Yao Y, Pan Y, Wen X & Ma L (2017) 'Suppression of MAPK11 or HIPK3 reduces mutant Huntingtin levels in Huntington's disease models' Cell Research 27, (12) 1441-1465 , DOI Open access

Key publications are highlighted

Journals
Articles
Ding Y, Xing D, Fei Y, Luo S & Lu B (2024) 'Perspectives of autophagy-tethering compounds (ATTECs) in drug discovery' Medicine Plus 1, (1) 100004-100004 Publisher Site , DOI
Barrow ER, Valionyte E, Baxter CR, Yang Y, Herath S, O’Connell WA, Lopatecka J, Strachan A, Woznica W & Stephenson HN (2024) 'Discovery of SQSTM1/p62-dependent P-bodies that regulate the NLRP3 inflammasome' Cell Reports 43, (3) 113935-113935 Publisher Site , DOI
Kelly J, Moyeed R, Carroll C, Luo S & Li X (2023) 'Blood biomarker-based classification study for neurodegenerative diseases' Scientific Reports 13, (1) , DOI Open access
Pan Y, Lu J, Feng X, Lu S, Yang Y, Yang G, Tan S, Wang L, Li P & Luo S (2023) 'Gelation of cytoplasmic expanded CAG RNA repeats suppresses global protein synthesis' Nature Chemical Biology 19, (11) 1372-1383 , DOI Open access
Valionyte E, Barrow ER, Baxter CR & Luo S (2022) 'A dominant-negative regulatory mechanism of SQSTM1 droplets-based autophagy' Autophagy 18, (4) 935-936 , DOI
Valionyte E, Yang Y, Griffiths SA, Bone AT, Barrow ER, Sharma V, Lu B & Luo S (2021) 'The caspase-6–p62 axis modulates p62 droplets based autophagy in a dominant-negative manner' Cell Death & Differentiation , DOI Open access
Fu Y, Chen N, Wang Z, Luo S, Ding Y & Lu B (2021) 'Degradation of lipid droplets by chimeric autophagy-tethering compounds' Cell Research 31, (9) 965-979 , DOI Open access
Klionsky DJ, Abdel-Aziz AK, Abdelfatah S, Abdellatif M, Abdoli A, Abel S, Abeliovich H, Abildgaard MH, Abudu YP & Acevedo-Arozena A (2021) 'Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)<sup>1</sup>' Autophagy 17, (1) 1-382 , DOI Open access
Li Z, Zhu Y-T, Xiang M, Qiu J-L, Luo S-Q & Lin F (2020) 'Enhanced lysosomal function is critical for paclitaxel resistance in cancer cells: reversed by artesunate' Acta Pharmacologica Sinica 42, (4) 624-632 , DOI
Kelly J, Moyeed R, Carroll C, Luo S & Li X (2020) 'Genetic networks in Parkinson&#x2019;s and Alzheimer&#x2019;s disease' Aging , DOI Open access
Roberts SL, Evans T, Yang Y, Fu Y, Button RW, Sipthorpe RJ, Cowan K, Valionyte E, Anichtchik O & Li H (2019) 'Bim contributes to the progression of Huntington's disease-associated phenotypes' Human Molecular Genetics , DOI Open access
Valionyte E, Yang Y, Roberts SL, Kelly J, Lu B & Luo S (2019) 'Lowering Mutant Huntingtin Levels and Toxicity: Autophagy-Endolysosome Pathways in Huntington's Disease' Journal of Molecular Biology 432, (8) 2673-2691 , DOI
Fan RZ, Guo M, Luo S, Cui M & Tieu K (2019) 'Exosome release and neuropathology induced by α-synuclein: new insights into protective mechanisms of Drp1 inhibition' Acta Neuropathologica Communications 7, (1) , DOI Open access
Li Z, Wang C, Wang Z, Zhu C, Li J, Sha T, Ma L, Gao C, Yang Y & Sun Y (2019) 'Allele-selective lowering of mutant HTT protein by HTT–LC3 linker compounds' Nature 575, (7781) 203-209 , DOI Open access
Yang Y, Valionyte E, Kelly J & Luo S (2019) 'Histone H3F3/H3.3 chaperone DAXX converts to modulate SQSTM1 phase condensation for NFE2L2 activation' Autophagy 16, (1) 171-172 , DOI
Yang Y, Willis TL, Button RW, Strang CJ, Fu Y, Wen X, Grayson PRC, Evans T, Sipthorpe RJ & Roberts SL (2019) 'Cytoplasmic DAXX drives SQSTM1/p62 phase condensation to activate Nrf2-mediated stress response' Nature Communications 10, (1) 0-0 , DOI Open access
Lin F & Luo S (2019) 'Mitochondria in neurodegenerative diseases' CNS Neuroscience and Therapeutics 25, (7) 813-815 , DOI Open access
Cowan K, Anichtchik O & Luo S (2019) 'Mitochondrial integrity in neurodegeneration' CNS Neuroscience and Therapeutics 25, (7) 825-836 , DOI Open access
Singer D, Thamm K, Zhuang H, Karbanová J, Gao Y, Walker JV, Jin H, Wu X, Coveney CR & Marangoni P (2018) 'Prominin-1 controls stem cell activation by orchestrating ciliary dynamics' EMBO Journal 38, (2) 0-0 Author Site , DOI Open access
Feng X, Luo S & Lu B (2018) 'Conformation Polymorphism of Polyglutamine Proteins' Trends in Biochemical Sciences 43, (6) 424-435 , DOI
Song H, Li H, Guo S, Pan Y, Fu Y, Zhou Z, Li Z, Wen X, Sun X & He B (2018) 'Targeting Gpr52 lowers mutant HTT levels and rescues Huntington's disease-associated phenotypes' Brain 141, (6) 1782-1798 Author Site , DOI Open access
Yu M, Fu Y, Liang Y, Song H, Yao Y, Wu P, Yao Y, Pan Y, Wen X & Ma L (2017) 'Suppression of MAPK11 or HIPK3 reduces mutant Huntingtin levels in Huntington's disease models' Cell Research 27, (12) 1441-1465 , DOI Open access
Button RW & Luo S (2017) 'The formation of autophagosomes during lysosomal defect: A new source of cytotoxicity' Autophagy 1-2 , DOI Open access
Button RW, Roberts SL, Willis TL, Hanemann CO & Luo S (2017) 'Accumulation of autophagosomes confers cytotoxicity' Journal of Biological Chemistry 13599-13614 , DOI Open access
Liu X, Li Y, Wang X, Xing R, Liu K, Gan Q, Tang C, Gao Z, Jian Y & Luo S (2017) 'The BEACH-containing protein WDR81 coordinates p62 and LC3C to promote aggrephagy' The Journal of Cell Biology 216, (5) 1301-1320 , DOI Open access
Button RW, Vincent JH, Strang CJ & Luo SHOUQING (2016) 'Dual PI-3 kinase/mTOR inhibition impairs autophagy flux and induces cell death independent of apoptosis and necroptosis' Oncotarget 7, (5) 5157-5175 , DOI Open access
Klionsky DJ, Abdelmohsen K, Abe A, Abedin MJ, Abeliovich H, Acevedo Arozena A, Adachi H, Adams CM, Adams PD & Adeli K (2016) 'Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)' Autophagy 12, (1) 1-222 , DOI
Zhuang H, Hu D, Singer D, Walker JV, Nisr RB, Tieu K, Ali K, Tredwin C, Luo S & Ardu S (2015) 'Local anesthetics induce autophagy in young permanent tooth pulp cells' Cell Death Discovery 1, Author Site Open access
Button RW, Luo S & Rubinsztein DC (2015) 'Autophagic activity in neuronal cell death' Neuroscience Bulletin 31, (4) 382-394 , DOI
Lin F, Ghislat G, Luo S, Renna M, Siddiqi F & Rubinsztein DC (2015) 'XIAP and cIAP1 amplifications induce Beclin 1-dependent autophagy through NFκB activation' Hum Mol Genet 24, (10) 2899-2913 Author Site , DOI Open access
Button RW, Lin F, Ercolano E, Vincent JH, Hu B, Hanemann CO & Luo S (2014) 'Artesunate induces necrotic cell death in schwannoma cells' Cell Death Dis 5, (10) Author Site , DOI Open access
Toh PPC, Luo S, Menzies FM, Raskó T, Wanker EE & Rubinsztein DC (2013) 'Myc inhibition impairs autophagosome formation' Hum Mol Genet 22, (25) 5237-5248 Author Site , DOI
Wu J, Jiang H, Luo S, Zhang M, Zhang Y, Sun F, Huang S & Li H (2013) 'Caspase mediated cleavage of C53/LZAP protein causes abnormal microtubule bundling and rupture of the nuclear envelope' Cell Research 23, (5) 691-704 , DOI
Luo S, Garcia-Arencibia M, Zhao R, Puri C, Toh PPC, Sadiq O & Rubinsztein DC (2012) 'Bim inhibits autophagy by recruiting Beclin 1 to microtubules' Molecular Cell 47, (3) 359-370 , DOI
Sarkar S, Korolchuk VI, Renna M, Imarisio S, Fleming A, Williams A, Garcia-Arencibia M, Rose C, Luo S & Underwood BR (2011) 'Complex inhibitory effects of nitric oxide on autophagy' Mol Cell 43, (1) 19-32 , DOI
Ravikumar B, Sarkar S, Davies JE, Futter M, Garcia-Arencibia M, Green-Thompson ZW, Jimenez-Sanchez M, Korolchuk VI, Lichtenberg M & Luo S (2010) 'Regulation of mammalian autophagy in physiology and pathophysiology' Physiol Rev 90, (4) 1383-1435 Author Site , DOI
Yang H, Liu C, Zhong Y, Luo S, Monteiro MJ & Fang S (2010) 'Huntingtin interacts with the cue domain of gp78 and inhibits gp78 binding to ubiquitin and p97/VCP' Plos One 26;5, (1)
Luo S, Eriguchi M, Mizuta H, Luo S, Kuroda Y, Hara H & Rubinsztein DC (2009) 'alpha Pix enhances mutant huntingtin aggregation' Journal of the Neurological Sciences 290, 80-85
Luo S & Rubinsztein DC (2009) 'Apoptosis blocks Beclin 1-dependent autophagosome synthesis - an effect rescued by Bcl-xL' Cell Death and Differentiation 17, 268-277 , DOI
Luo S & Rubinsztein DC (2009) 'Huntingtin promotes cell survival by preventing Pak2 cleavage' Journal of Cell Science 122, 875-885 , DOI
Luo S, Mizuta H & Rubinsztein DC (2008) 'p21-activated kinase 1 promotes soluble mutant huntingtin self-interaction and enhances toxicity' Human Molecular Genetics 15, 895-905
Yang H, Zhong X, Ballar P, Luo S, Shen Y, Rubinsztein DC, Monteiro MJ & fang S (2007) 'The extended quality control role of the ER‐anchored ubiquitin ligase Hrd1 in the targeting of expanded huntingtin for degradation' The FASEB Journal 21, (6) , DOI
Yang H, Zhong X, Ballar P, Luo S, Shen Y, Rubinsztein DC, Monteiro MJ & Fang S (2006) 'Ubiquitin ligase Hrd1 enhances the degradation and suppresses the toxicity of polyglutamine-expanded huntingtin' Experimental Cell Research 313, 538-550
Berger Z, Davies JE, Luo S, Pasco MY, Majoul I, O'Kane CJ & Rubinsztein DC (2005) 'Deleterious and protective properties of an aggregate-prone protein with a polyalanine expansion' Human Molecular Genetics 15, 453-465
Luo S, Vacher C, Davies JE & Rubinsztein DC (2005) 'Cdk5 phosphorylation of huntingtin reduces its cleavage by caspases: implications for mutant huntingtin toxicity' Journal of Cell Biology 169, 647-656
Jiang H, Luo S & Li H (2005) 'Cdk5 activator-binding protein C53 regulates apoptosis induced by genotoxic stress via modulating the G2/M DNA damage checkpoint' Journal of Biological Chemistry 280, 20651-20659
Wu J, Luo S, Jiang H & Li H (2005) 'Mammalian CHORD-containing protein 1 is a novel heat shock protein 90-interacting protein' FEBS Letters. 579, 421-426
Ravikumar B, Vacher C, Berger Z, Davies JE, Luo S, Oroz LG, Scaravilli F, Easton DF, Duden R & O'Kane CJ (2004) 'Inhibition of mTOR induces autophagy and reduces toxicity of polyglutamine expansions in fly and mouse models of Huntington disease' Nature Genetics 585-595
Luo S, Zheng D, Rao Q & Wu K (2000) 'Analysis of the Ligand-binding domain of Macrophage colony-stimulating receptor' Chinese Science Bulletin 45, 1191-1196
Luo S, Zheng D & Liu Y (2000) 'Expression of rhM-CSFR in E.coli and analysis of its ligand-binding affinity' Chin J Biochem Mol Biol 16, 443-447
Luo S, Liu Y & Zheng D (1999) 'Expression of rhM-CSFR in insect cells and analysis of its ligand-binding affinity' Chin J Biochem Mol Biol 15, 709-714
Luo S & Zheng D (1998) 'Signal transduction pathways medicated by colony stimulating factor-1 receptor' Chinese Science Bulletin, 43, 969-973
Reviews
Luo S & Rubinsztein DC (2012) 'BCL2L11/BIM: a novel molecular link between autophagy and apoptosis' Autophagy 9, (1) 104-105
Moreau K, Luo S & Rubinsztein DC (2010) 'Cytoprotective roles for autophagy' Curr Opin Cell Biol 22, 206-211
Ravikumar B, Futter M, Jahreiss L, Korolchuk VI, Lichtenberg M, Luo S, Massey DCO, Menzies FM, Narayanan U & Renna M (2009) 'Mammalian macroautophagy at a glance' Journal of Cell Science 122, 1707-1711 , DOI
Luo S & Rubinsztein DC (2007) 'Atg5 and Bcl-2 provide novel insights into the interplay between apoptosis and autophagy' Cell Death Differ 14, 1247-1250
Chapters
Evans T, Button R, Anichtchik O & Luo S (2018) 'Visualization and Measurement of Multiple Components of the Autophagy Flux' Autophagy in Differentiation and Tissue Maintenance Springer New York 1-12 , DOI
Personal

Personal

Conferences organised

  • November 2019, 1st Sino-UK neuroscience meeting, Shenzhen, China
  • September 2019, The 25th Annual Conference of CLSS, London, UK
  • April 2017, The London PhD Network (LPN) 5th Symposium: Neuroscience and CRYO-EM, London, UK
  • October 2016, Collaborative strategies to study neurodegeneration, Swindon, UK